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Little is known about prevalence and predictors of myocardial infarction with non-obstructive coronary arteries (MINOCA) in Fabry disease (FD) and hypertrophic cardiomyopathy (HCM). We assessed and compared the prevalence and predictors of MINOCA in a large cohort of HCM and FD patients.In this multicenter, retrospective study we enrolled 2870 adult patients with HCM and 267 with FD. The only exclusion criterion was documented obstructive coronary artery disease. MINOCA was defined according to guidelines. For each patient we collected clinical, ECG and echocardiographic data recorded at initial evaluation.Overall, 36 patients had MINOCA during a follow-up period of 4.5 ± 11.2 years. MINOCA occurred in 16 patients with HCM (0.5%) and 20 patients with FD (7.5%; p lt; 0.001). The difference between the 2 groups was highly significant, also after adjustment for the main clinical, ECG and echocardiographic variables (OR 6.12; 95%CI 2.80-13.3; p lt; 0.001). In the FD population MINOCA occurred in 17 out of 96 patients with left ventricle hypertrophy (LVH, 17.7%) and in 3 out of 171 patients without LVH (1.7%; OR 12.0; 95%CI 3.43-42.3; p lt; 0.001). At multivariable analysis, voltage criteria for LVH at ECG (OR 7.3; 95%CI 1.93-27.7; p = 0.003) and maximal LV wall thickness at echocardiography (OR 1.15; 95%CI 1.05-1.27; p = 0.002) maintained an independent association with MINOCA. No major significant differences were found in clinical, ECG and echocardiographic findings between HCM patients with or without MINOCA.MINOCA was rare in HCM patients, and 6-fold more frequent in FD patients. MINOCA may be considered a red flag for FD and aid in the differential diagnosis from HCM.

Aims To perform evaluation of widely embraced bone scintigraphy-based non-biopsy diagnostic criteria (NBDC) for ATTR amyloid cardiomyopathy (ATTR-CM) in clinical practice, and to refine serum free light chain (sFLC) ratio cut-offs that reliably exclude monoclonal gammopathy (MG) in chronic kidney disease. Methods and results A multi-national retrospective study of 3354 patients with suspected or histologically proven cardiac amyloidosis (CA) referred to specialist centres from 2015 to 2021; evaluations included radionuclide bone scintigraphy, serum and urine immunofixation, sFLC assay, eGFR measurement and echocardiography. Seventy-nine percent (1636/2080) of patients with Perugini grade 2 or 3 radionuclide scans fulfilled NBDC for ATTR-CM through absence of a serum or urine monoclonal protein on immunofixation together with a sFLC ratio falling within revised cut-offs incorporating eGFR; 403 of these patients had amyloid on biopsy, all of which were ATTR type, and their survival was comparable to non-biopsied ATTR-CM patients (p = 0.10). Grade 0 radionuclide scans were present in 1091 patients, of whom 284 (26%) had CA, confirmed as AL type (AL-CA) in 276 (97%) and as ATTR-CM in only one case with an extremely rare TTR variant. Among 183 patients with grade 1 radionuclide scans, 122 had MG of whom 106 (87%) had AL-CA; 60/61 (98%) without MG had ATTR-CM. Conclusion The NBDC for ATTR-CM are highly specific [97% (95% CI 0.91-0.99)] in clinical setting, and diagnostic performance was further refined here using new cut-offs for sFLC ratio in patients with CKD. A grade 0 radionuclide scan all but excludes ATTR-CM but occurs in most patients with AL-CA. Grade 1 scans in patients with CA and no MG are strongly suggestive of early ATTR-type, but require urgent histologic corroboration.

Fabry disease (FD, OMIM 301500) is an X-linked lysosomal storage disease caused by pathogenic variants in the GLA gene. Cardiac involvement is common in FD and is responsible for impaired quality of life and premature death. The classic cardiac involvement is a nonobstructive form of hypertrophic cardiomyopathy, usually manifesting as concentric left ventricular hypertrophy, with subsequent arrhythmogenic intramural fibrosis. Treatment of patients with FD should be directed to prevent the disease progression to irreversible organ damage and organ failure. The aim of this review is to describe the current state of knowledge regarding cardiovascular involvement in FD, focusing on clinical and instrumental features, cardiovascular management, and targeted therapy.

Cardiac magnetic resonance (CMR) has become an essential tool for the evaluation of patients affected or at risk of developing cardiomyopathies (CMPs). In fact, CMR not only provides precise data on cardiac volumes, wall thickness, mass and systolic function but it also a non-invasive characterization of myocardial tissue, thus helping the early diagnosis and the precise phenotyping of the different CMPs, which is essential for early and individualized treatment of patients. Furthermore, several CMR characteristics, such as the presence of extensive LGE or abnormal mapping values, are emerging as prognostic markers, therefore helping to define patients’ risk. Lastly new experimental CMR techniques are under investigation and might contribute to widen our knowledge in the field of CMPs. In this perspective, CMR appears an essential tool to be systematically applied in the diagnostic and prognostic work-up of CMPs in clinical practice. This review provides a deep overview of clinical applicability of standard and emerging CMR techniques in the management of CMPs.

AimsDiagnosis of arrhythmogenic cardiomyopathy (ACM) may be challenging, as it comprises diverse phenotypes (right dominant, biventricular, and left dominant), and each may overlap with other clinical entities. The issue of differential diagnosis with conditions mimicking ACM has been previously highlighted; however, a systematic analysis of ACM diagnostic delay, and of its clinical implications, is lacking.Methods and resultsData of all ACM patients from three Italian Cardiomyopathy Referral Centres were reviewed to assess the time from first medical contact to definitive ACM diagnosis; a significant diagnostic delay was defined as a time to ACM diagnosis ≥2 years. Baseline characteristics and clinical course of patients with and without diagnostic delay were compared. Of 174 ACM patients, 31% experienced diagnostic delay, with a median time to diagnosis of 8 years (20% in right-dominant ACM, 33% in left-dominant ACM, and 39% in biventricular). Patients with diagnostic delay, when compared with those without, more frequently exhibited an ACM phenotype with left ventricular (LV) involvement (74 vs. 57%, P = 0.04) and a specific genetic background (none had plakophilin-2 variants). The most common initial (mis)diagnoses were dilated cardiomyopathy (51%), myocarditis (21%), and idiopathic ventricular arrhythmia (9%). At follow-up, all-cause mortality was greater in those with diagnostic delay (P = 0.03).ConclusionDiagnostic delay is common in patients with ACM, particularly in the presence of LV involvement, and is associated with greater mortality at follow-up. Clinical suspicion and increasing use of tissue characterization by cardiac magnetic resonance in specific clinical settings are of key importance for the timely identification of ACM.

Background Anderson Fabry disease (AFD) is a rare X-linked lysosomal storage disorder caused by deficient activity of α-galactosidase A bringing to intracellular accumulation of globotriaosylceramide (Gb3) in affected tissues, including heart. Progressive cardiac involvement has shown to cause electrocardiographic modifications in these patients. Treatment with enzyme replacement therapy (ERT) or chaperone therapy has demonstrated to decrease Gb3 levels in the heart, but little is known about its influence on ECG evolution. Purpose to gain new insights about ECG evolution in AFD patients on and off specific disease therapy and to assess its potential role in the diagnosis and the follow-up of these patients. Methods we analysed the ECG evolution of a multicentre study cohort of 170 patients with a diagnosis of AFD (64 males 38%, median age 46±15 years) for a median follow-up of 64±48 months, dividing them into patients off (group A, N=63) and on (group B, N= 107) specific therapy. Results the two groups did not differ as regard age at baseline (47±14 vs 44±12 years; p=0,171) but patients off specific disease therapy (group A) showed lower prevalence of male sex [13(21%) vs 51(48%); p= Conclusion We observed ECG progression despite specific disease therapy in 29% of patients of group B showing a potential role of ECG as a marker of cardiac specific response to therapy in these patients. Differently we detected ECG progression in 14% of patients off specific therapy, which is consistent with their less advanced cardiac involvement (lower prevalence of male sex, classic phenotype and lower maximum wall thickness), suggesting that ECG could be an important tool to detect an initial cardiac involvement in these patients even in absence of hypertrophy. The absence of left bundle branch blocks in the two groups compared with a significant prevalence of complete and incomplete right conduction delay could suggest a prevalent involvement of the right bundle branch in these patients and could represent a red flag for the diagnosis of AFD.

Man, 72 years old, smoker, hypertensive and dyslipidemic, came to our clinic suspected of heart disease with a hypertrophic phenotype. In anamnesis there was a recent hospitalization for heart failure in the course of undated atrial fibrillation. During hospitalization because of the presence of antero-septal and lateral QS complexes, a coronary disease was excluded by coronary angiography while the echocardiogram showed a left ventricle with moderate concentric wall thickening, LVEF 38% with a restrictive transmitral pattern. The patient was discharged on therapy with ramipril, bisoprolol, canrenone, furosemide and rivaroxaban with an electrical cardioversion program which had been subsequently ineffective. At the time of the first evaluation the patient was symptomatic of dyspnea in functional class NYHA III, he also reported in anamnesis a progressive reduction of exercise tolerance for about two years and a previous surgery for bilateral carpal tunnel syndrome 5 years earlier. The echocardiogram showed concentric parietal thickening in the presence of granular sparkling, apical sparing, thickening of the valvular apparatus and reduced GLS (- 12%) which led to a suspect of cardiac amyloidosis. To complete the diagnosis, the patient underwent: total-body bone scan with 99-Tc-DPD (Perugini score = 2); assay of serum kappa and lambda light chains (negative), serum and urinary immunofixation (negative), NT-proBNP (980 pg / mL) and a determination of troponin I (32 ng / L) which showed a picture of transthyretin cardiac amyloidosis. The genetic sampling confirmed the presence of the Ile68Leu transthyretin mutation and a neurological evaluation with electromyography ruled out a peripheral polyneuropathy. During follow-up the patient presented a worsening of clinical and instrumental pattern despite the progressive uptitration of diuretic therapy and the addition of metolazone with a simultaneous deterioration of left ventricular dysfunction (LVEF 30%) at echocardiogram. Therefore, the patient's case and possible therapeutic strategies were discussed collectively as it was not possible to access conventional therapies for cardiac amyloidosis with Tafamidis, Inotersen and Patisiran due to the contextual functional class NYHA> II and the absence of polyneuropathy, not it was possible to undertake biventricular resynchronization in the absence of intraventricular block or to implement therapy for heart failure with reduced ejection fraction due to intolerance. As a last option, implantation of a cardiac contractility modulation device (CCM) was proposed and performed via right subclavicular. At the successive follow-up after implantation, the patient showed a slight clinical and instrumental improvement and it was possible to reduce the diuretic dose, discontinuing metolazone. The echocardiogram also showed a slight increase in LVEF (35%). The long-term outpatient evaluation of the patient is currently underway with the aim of undertaking specific therapy with Tafamidis if the prescription criteria are met. Family screening has started. Conclusion the present clinical case represents an example of the application of alternative and potentially effective therapeutic strategies in patients with cardiac amyloidosis not susceptible to conventional pharmacological treatments.

Aims The prognostic role of bone tracer uptake in transthyretin cardiac amyloidosis (ATTR-CA) is controversial. The study investigated the potential prognostic significance of biventricular (BiV) uptake in ATTR-CA. Methods Consecutive ATTR-CA patients who had cardiac scintigraphy with acquisition of planar and single-photon emission computed tomography (SPECT) images from the National Amyloidosis Centre (NAC) and four Italian centres were included. Planar BiV uptake was defined in presence of right ventricle (RV) uptake and graded in combination with SPECT imaging. The primary outcome was all-cause mortality. Results Among 1422 patients with ATTR-CA, BiV uptake was found in 85% of cases on planar scintigraphy and in 100% of cases on SPECT images. During a median follow-up of 39 months, BiV uptake at planar scintigraphy was associated with a higher all-cause mortality compared to isolated LV uptake (40.5% vs 10.7%, p Conclusions Planar RV uptake leading to BiV uptake identified ATTR-CA patients with worse outcome, potentially serving as a novel prognostic marker.

Background The prevalence and course of heart failure (HF) in arrhythmogenic cardiomyopathy (ACM) is unresolved, and previous studies have mostly focused on the right-dominant variant of the disease, less prone to HF. Conversely, ACM variants with left ventricular (LV) involvement are now increasingly recognized, often initially ‘mis-diagnosed’ as dilated cardiomyopathy. Aim of this study was therefore to describe the prevalence and clinical course of advance HF in the full clinical spectrum of ACM. Methods We retrospectively reviewed records of all ACM patients diagnosed before 2021 from 3 Italian Cardiomyopathy Referral Centres (Azienda Ospedaliero Universitaria Careggi; Policlinico Sant’Orsola; Azienda Ospedaliero Universitaria Sant’Andrea). LV involvement was diagnosed in the presence of subepicardial late gadolinium enhancement (LGE) in at least 3 contiguous segments in the same short-axis slice at cardiac magnetic resonance, independent of whether it fulfilled the 2010 Task Force criteria for right-dominant ACM (biventricular ACM) or not (left-dominant ACM); in this latter case, diagnosis was reached after careful exclusion of other differential diagnosis, and only when at least one of the following features was present: likely pathogenic/pathogenic genetic variant associated with ACM; familial history of ACM; electrocardiographic abnormalities suggestive of ACM with LV involvement. Advanced HF was defined as NYHA functional class III/IV and/or referral for heart transplantation. Median follow-up was 6 years. Results Forty-four out of 174 ACM patients (25%) developed advanced HF: 10 right-dominant ACM and 34 with LV involvement. Twenty ACM patients were initially diagnosed with dilated cardiomyopathy; as such, development of advanced HF in 17 cases preceded the diagnosis of ACM. Five patients were diagnosed with ACM after heart transplantation, by histological examination. In the other 22, median time from ACM diagnosis to advanced HF development was 4 years. As compared to those without, advanced HF patients were more likely to present LV involvement. During clinical course, 20 (46%) advanced HF patients received at least one appropriate ICD intervention, with 13 experiencing an electrical storm. Twenty-six (59%) patients required HF-related hospitalization, and 32 (72%) were referred for heart transplantation with 25 ultimately receiving it. ACM patients with advanced HF, compared to those without, experienced a higher rate of mortality (36% vs. 6%; OR 3.5 [95%CI: 1.4-8.7], p=0.01) and ventricular arrhythmic events (41% vs. 11%; OR 2.4 [95%CI: 1.1-5.0], p=0.02). Conclusions Advanced HF progression in ACM is not rare, and occurs more frequently in variants with LV involvement. Advanced HF is associated with increased mortality and arrhythmic risk.

Background Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder that have gained attention due to the availability of therapeutic options. Disease specific therapy (DST), either by enzyme replacement therapy or oral pharmacological chaperone, is the mainstay for AFD treatment. Although its widespread use, few data are available on the electrocardiographic variations associated with DST. Purpose To evaluate ECG findings and variations in AFD according to time duration of DST, comparing patients under long-term therapy with naïve patients starting therapy during follow-up. Methods One-hundred-seventy-nine AFD patients, ≥18 years old, with 2 readable ECGs, were recruited in the present multicentre study cohort. Two patients were excluded due to pacemaker (PM) implantation. Only patients on DST (n=107) were considered for final cohort and divided into 2 groups according to therapy duration: Group A (n=42) included patients treated for ≥12 months at the time of first evaluation, whereas Group B patients (n=65) started therapy during follow-up. Results Group A and Group B had not significant difference in terms of age at presentation (48[39-60] vs 48[36-56]years; p=0.856) and maximal wall thickness (13[11-15] vs 13[11-18]mm; p=0.090) whereas they differed for male prevalence (61% vs 38%; p=0.029) and classic phenotype (86% vs 29%; p During the follow-up (57[60-28] months for Group A vs 70[37-85] months for Group B; p=0.152), both groups developed electrocardiographic alterations (38% vs 23%; p=0.127). Specifically, in GroupA, 4 (10%) patients presented AF, 1 (2%) AVB, 7 (17%) complete or incomplete RBBB, 4 (10%) LAFB, 1 (2%) LVH and 8 (19%) repolarization abnormalities. In Group B, 2 (3%) developed AF, 1 (2%) AVB, 7 (11%) complete or incomplete RBBB, 2(3%) LVH and 11(17%) repolarization abnormalities; none developed LAFB. Conclusions In this AFD cohort, both patients on chronic DST (Group A) and patients who started treatment during follow-up (Group B) developed ECG alterations. Treatment status didn't affect considerably the developing of ECG abnormalities and DST did not prevent ECG changes. ECG alterations during the follow-up were more frequent in Group A (38% vs 23%), mainly composed by classic phenotype and male patients, thus supporting a prompt start of therapy at an early stage.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome that has become a global health issue, with mortality ranging from 53% to 74% at 5 years. It is defined as the presence of signs and symptoms of heart failure associated with left ventricular ejection fraction greater than or equal to 50%. The definition and diagnosis of HFpEF in patients with unexplained dyspnea remain a clinical challenge in the absence of a unique diagnostic algorithm universally recognized. Clinical trials conducted so far did not show a significant improvement of prognosis, but forthcoming therapies could provide innovative solutions.

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Systemic amyloidosis is a hereditary or acquired disease characterized by deposition of amyloid insoluble fibrils into body organs and tissues, causing structural abnormalities and organ dysfunction, i.e. heart failure. This disease is classified according to the precursor protein involved; immunoglobulin light chains, transthyretin and apolipoprotein A1 underlie the cardiac involvement. Amyloid cardiomyopathy is characterized by symmetric biventricular hypertrophy, preserved systolic function, and pronounced diastolic dysfunction. Although transthyretin-related cardiac amyloidosis has always been considered a rare disease, in the last few years it has been found to be one of the most common causes of hypertrophic cardiomyopathy, thanks to better diagnostic algorithms and considerable improvements in cardiac imaging. Achieving an early diagnosis is a challenge for the modern cardiologist since new disease-modifying therapies have been developed in recent years. This article aims to answer to the main questions about transthyretin-related cardiac amyloidosis: when to suspect it, how to diagnose it and how to treat it.

The echocardiographic parameters required for a comprehensive assessment of cardiac masses (CMs) are still largely unknown.To identify and integrate the echocardiographic features of CMs that can accurately predict malignancy.Observational cohort study of 286 consecutive patients who underwent a standard echocardiographic assessment for suspected cardiac mass in Bologna University Hospital between 2004 and 2022. A definitive diagnosis was achieved by histological examination or, in case of cardiac thrombi, with radiological evidence of thrombus resolution after an appropriate anticoagulant treatment. Logistic and multivariable regression analysis was performed to confirm the ability of 6 echocardiographic parameters to discriminate malignant from benign masses. The unweighted count of these parameters was used as a numerical score, ranging from 0 to 6, with a cut-off of3 balancing sensitivity and specificity with respect to the histological diagnosis of malignancy. Classification tree analysis (CTA) was used to determine the ability of echocardiographic parameters to discriminate sub-groups of patients with a differential risk of malignancy.Benign masses were more frequently pedunculated, mobile, and adherent to the interatrial septum (p0.001). Malignant masses showed a greater diameter and exhibited a higher frequency of irregular margins, an inhomogeneous appearance, sessile implantation, polylobate shape, and pericardial effusion (p0.001). Infiltration, moderate-severe pericardial effusion, non-left localization, sessile, polylobate, and inhomogeneity were confirmed to be independent predictors of malignancy in both univariate and multivariable models. The predictive ability of the unweighted count of3 was very high (0.90) and similar to that of the previously published weighted score. The CTA generated an algorithm in which infiltration was the best discriminator of malignancy, followed by non-left localization and sessile shape. The percentage correctly classified by the CTA as malignant was 87.5%. Agreement between observer readings and cardiac mass histology ranged between 85.1-91.5%. The presence of at least 3 echocardiographic parameters was associated with a lower survival.In the approach to CM, some echocardiographic parameters can serve as markers to accurately predict malignancy, thereby informing the need for second-level investigations and minimizing the diagnostic delay in such a complex clinical scenario.

Aim: To evaluate short-term changes in tricuspid regurgitation (TR) after transcatheter edge-to-edge mitral valve repair (M-TEER) in secondary mitral regurgitation (SMR), their predictors and impact on mortality. Methods and results: This is a retrospective analysis of SMR patients undergoing successful M-TEER (post-procedural mitral regurgitation ≤2+) at 13 European centres. Among 503 patients evaluated 79 (interquartile range [IQR] 40-152) days after M-TEER, 173 (35%) showed ≥1 degree of TR improvement, 97 (19%) had worsening of TR, and 233 (46%) remained unchanged. Smaller baseline left atrial diameter and residual mitral regurgitation 0/1+ were independent predictors of TR ≤2+ after M-TEER. There was a significant association between TR changes and New York Heart Association class and pulmonary artery systolic pressure decrease at echocardiographic re-assessment. At a median follow-up of 590 (IQR 209-1103) days from short-term echocardiographic re-assessment, all-cause mortality was lower in patients with improved compared to those with unchanged/worsened TR (29.6% vs. 42.3% at 3 years; log-rank p = 0.034). Baseline TR severity was not associated with mortality, whereas TR 0/1+ and 2+ at short-term follow-up was associated with lower all-cause mortality compared to TR 3/4+ (30.6% and 35.6% vs. 55.6% at 3 years; p < 0.001). A TR ≤2+ after M-TEER was independently associated with a 42% decreased risk of mortality (p = 0.011). Conclusion: More than one third of patients with SMR undergoing successful M-TEER experienced an improvement in TR. Pre-procedural TR was not associated with outcome, but a TR ≤2+ at short-term follow-up was independently associated with long-term mortality. Optimal M-TEER result and a small left atrium were associated with a higher likelihood of TR ≤2+ after M-TEER.

Childhood hypertrophic cardiomyopathy; Outcomes; Phenotype Miocardiopatía hipertrófica infantil; Resultados; Fenotipo Miocardiopatia hipertròfica infantil; Resultats; Fenotip Background Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized. Objectives The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years. Methods Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years. Results At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age. Conclusions Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages. This work was supported by the British Heart Foundation (grant FS/16/72/32270) to Drs Norrish and Kaski. This work is (partly) funded by the National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre. Dr Norrish is supported by Great Ormond Street Hospital Children’s Charity. Drs Field and Kaski are supported by Max’s Foundation and Great Ormond Street Hospital Children’s Charity. Dr Kaski is supported by a Medical Research Council–National Institute for Health Research Clinical Academic Research Partnership award. This work was financially supported by the Foundation for Paediatric Research of Finland (Dr Ojala). Dr Fernandez has received speaker fees from Sanofi-Genzyme. Dr Kubus is supported by MH CZ – DRO, Motol University Hospital (00064203). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Severe mitral valve regurgitation (MR) carries a significant burden both in prognosis and quality of life of patients, as well as on healthcare systems, with high rates of hospitalization for heart failure. While mitral valve surgery constitutes the first-line treatment option for primary MR in suitable patients, surgical treatment for secondary severe MR remains controversial, with a substantial lack of evidence on a survival benefit. In recent decades, percutaneous mitral valve repair has emerged as an alternative treatment for patients deemed not suitable for surgery. Among several devices under development or evaluation, the MitraClip system is the most widespread and is supported by the strongest evidence. While the role of MitraClip in patients with chronic primary MR who are not deemed suitable for surgery is well established, with consistent data showing improvement in both prognosis and quality of life, MitraClip treatment in secondary MR is a rapidly evolving field. Two recent randomized clinical trials generated apparently controversial results but actually provided an interesting pathophysiologic frame that could help discerning patients who will benefit from the procedure versus patients who will not. In this review, we will discuss current treatment options for mitral regurgitation, focusing on percutaneous mitral valve repair with the MitraClip system.

Objectives: The aim of this study was to evaluate the outcome of transcatheter mitral valve repair (TMVr) in patients with cardiogenic shock and significant mitral regurgitation (MR). Background: Patients in cardiogenic shock with severe MR have a poor prognosis in the setting of conventional medical therapy. Because of its favorable safety profile, TMVr is being increasingly used as an acute therapy in this population, though its efficacy remains unknown. Methods: A multicenter, collaborative, patient-level analysis was conducted. Patients with cardiogenic shock and moderate to severe (3+) or severe (4+) MR who were not surgical candidates were treated with TMVr. The primary outcome was in-hospital mortality. Secondary outcomes included 90-day mortality, heart failure (HF) hospitalization, and the combined event rate of 90-day mortality and HF hospitalization following dichotomization by TMVr device success. Results: Between January 2011 and February 2019, 141 patients across 14 institutions met the inclusion criteria. In-hospital mortality occurred in 22 patients (15.6%), at 90 days in 38 patients (29.5%), and at one year in 55 patients (42.6%). Median length of hospital stay following TMVr was 10 days (interquartile range: 6 to 20 days). HF hospitalization occurred in 26 patients (18.4%) at a median of 73 days (interquartile range: 26 to 546 days). When stratified by TMVr procedural results, successful TMVr reduced rates of in-hospital mortality (hazard ratio [HR]: 0.36; 95% confidence interval [CI]: 0.13 to 0.98; p = 0.04), 90-day mortality (HR: 0.36; 95% CI: 0.16 to 0.78; p = 0.01), and the composite of 90-day mortality and HF hospitalization (HR: 0.41; 95% CI: 0.19 to 0.90; p = 0.03). Conclusions: TMVr may improve short- and intermediate-term mortality in high-risk patients with cardiogenic shock and moderate to severe MR. Randomized studies are needed to definitively establish MR as a therapeutic target in patients with cardiogenic shock.

Nonischemic-dilated cardiomyopathy (NIDCM) is an entity that gathers extremely heterogeneous diseases. This awareness, although leading to continuous improvement in survival, has increased the complexity of NIDCM patients' management. Even though the endorsed 'red-flags' approach helps clinicians in pursuing an accurate etiological definition in clinical practice, it is not clear when and how peripheral centers should interact with referral centers with specific expertise in challenging scenarios (e.g. postmyocarditis and genetically determined dilated cardiomyopathy) and with easier access to second-line diagnostic tools and therapies. This position paper will summarize each step in NIDCM management, highlighting the multiple interactions between peripheral and referral centers, from first-line diagnostic workup and therapy to advanced heart failure management and long-term follow-up.

Aim: To investigate the prevalence of amyloid cardiomyopathy (AC) and the diagnostic accuracy of echocardiographic red flags of AC among consecutive adult patients undergoing transthoracic echocardiogram for reason other than AC in 13 Italian institutions. Methods and results: This is an Italian prospective multicentre study, involving a clinical and instrumental work-up to assess AC prevalence among patients ≥55 years old with an echocardiogram suggestive of AC (i.e. at least one echocardiographic red flag of AC in hypertrophic, non-dilated left ventricles with preserved ejection fraction). The study was registered at ClinicalTrials.gov (NCT04738266). Overall, 381 patients with an echocardiogram suggestive of AC were identified among a cohort of 5315 screened subjects, and 217 patients completed the investigations. A final diagnosis of AC was made in 62 patients with an estimated prevalence of 29% (95% confidence interval 23%–35%). Transthyretin-related AC (ATTR-AC) was diagnosed in 51 and light chain-related AC (AL-AC) in 11 patients. Either apical sparing or a combination of ≥2 other echocardiographic red flags, excluding interatrial septum thickness, provided a diagnostic accuracy >70%. Conclusion: In a cohort of consecutive adults with echocardiographic findings suggestive of AC and preserved left ventricular ejection fraction, the prevalence of AC (either ATTR or AL) was 29%. Easily available echocardiographic red flags, when combined together, demonstrated good diagnostic accuracy.

Mitral valve prolapse is a relatively common disease with a good overall prognosis. However, in specific clinical and instrumental contexts, patients at high risk of ventricular arrhythmias and sudden cardiac death can be identified. Female sex, history of palpitations or syncope, bi-leaflet myxomatous valve, ECG repolarization abnormalities in the inferior leads, complex ventricular arrhythmias, left ventricular fibrosis detected by cardiac magnetic resonance correlate with a higher risk clinical profile. Additionally, morpho-functional abnormalities of the mitral valve annulus, particularly mitral annulus disjunction, may cause a mechanical stretch at the inferior basal ventricular wall and posterior papillary muscles, predisposing to myocardial fibrosis and arrhythmias. A risk stratification strategy is needed to identify patients with mitral valve prolapse and/or mitral annulus disjunction at high risk of arrhythmias; however, few data are available. Further prospective multicenter studies are warranted, focusing on medical therapy, the role of implantable cardioverter-defibrillators for primary prevention, efficacy of targeted catheter ablation or mitral valve surgery.

Background: we sought to review the evolution in the diagnosis and treatment of Arrhythmogenic Cardiomyopathy (ACM), a clinically multifaceted entity beyond the observation of ventricular arrhythmias, and the outcome of therapies aiming at sudden death prevention in a single center experience. Methods: retrospective analysis of the data of consecutive patients with an implanted cardioverter-defibrillator (ICD) and a confirmed diagnosis of ACM according to the proposed Padua Criteria, who were referred to our center from January 1992 to October 2021. Results: we enrolled 72 patients (66% males, mean age at implant 46 ± 16 years), 63.9% implanted for primary prevention. At the time of ICD implant, 29 (40.3%) patients had a right ventricular involvement, 24 (33.3%) had a dominant LV involvement and 19 (26.4%) had a biventricular involvement. After a median follow-up of 6,1 years [IQR: 2.5–9.9], 34 patients (47.2%) had 919 sustained episodes of ventricular arrhythmias (VA). 27 patients (37.5%) had 314 episodes of life-threatening arrhythmias (LT-VA), defined as sustained ventricular tachycardia ≥200 beats/min. Considering only the patients with an ICD capable of delivering ATP, 80.4% of VA and 65% of LT-VA were successfully terminated with ATP. 16 (22.2%) patients had an inappropriate ICD activation, mostly caused by atrial fibrillation, while in 9 patients (12.5%) there was a complication needing reintervention (in 3 cases there was a loss of ventricular sensing dictating lead revision). During the follow-up 11 (15.3%) patients died, most of them due to heart failure, and 8 (11.1%) underwent heart transplantation. Conclusions: ACM is increasingly diagnosed owing to heightened suspicion at ECG examination and to improved imaging technology and availability, though the diagnostic workflow is particularly challenging in the earliest disease stages. ICD therapy is the cornerstone of sudden death prevention, albeit its efficacy is not based on controlled studies, and VT ablation/medical therapy are complementary to this strategy. The high burden of ATP-terminated VA makes shock-only devices debatable. The progressive nature of ACM leads to severe biventricular enlargement and refractory heart failure, which pose significant treatment issues when a predominant RV dysfunction occurs owing to the reduced possibility for mechanical circulatory assistance.

ObjectivesTo describe a cohort of patients with arrhythmogenic left ventricular cardiomyopathy (ALVC), focusing on the spectrum of the clinical presentations.MethodsPatients were retrospectively evaluated between January 2012 and June 2020. Diagnosis was based on (1) ≥3 contiguous segments with subepicardial/midwall late gadolinium enhancement in the left ventricle (LV) at cardiac magnetic resonance plus a likely pathogenic/pathogenic arrhythmogenic cardiomyopathy (AC) associated genetic mutation and/or familial history of AC and/or red flags for ALVC (ie, negative T waves in V4-6/aVL, low voltages in limb leads, right bundle branch block like ventricular tachycardia) or (2) pathology examination of explanted hearts or autoptic cases suffering sudden cardiac death (SCD). Significant right ventricular involvement was an exclusion criterion.ResultsFifty-two patients (63% males, age 45 years (31–53)) composed the study cohort. Twenty-one (41%) had normal echocardiogram, 13 (25%) a hypokinetic non-dilated cardiomyopathy (HNDC) and 17 (33%) a dilated cardiomyopathy (DCM). Of 47 tested patients, 29 (62%) were carriers of a pathogenic/likely pathogenic DNA variant. Clinical contexts leading to diagnosis were SCD in 3 (6%), ventricular arrhythmias in 15 (29%), chest pain in 8 (15%), heart failure in 6 (12%) and familial screening in 20 (38%). Thirty patients (57%) had previously received a diagnosis other than ALVC with a diagnostic delay of 6 years (IQR 1–7).ConclusionsALVC is hidden in different clinical scenarios with a phenotypic spectrum ranging from normal LV to HNDC and DCM. Ventricular arrhythmias, chest pain, heart failure and SCD are the main clinical presentations, being familial screening essential for the affected relatives’ identification.